更新于：2024-11-01

H1 receptor x 5-LOX

更新于：2024-11-01

基本信息

关联

项与 H1 receptor x 5-LOX 相关的药物

Flezelastine hydrochloride

氟卓斯汀

靶点

5-LOX x H1 receptor

作用机制

5-LOX抑制剂 [+1]

在研机构-

原研机构

Meda AB

在研适应症-

非在研适应症

哮喘 [+2]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

Tagorizine

靶点

5-LOX x H1 receptor

作用机制

5-LOX抑制剂 [+1]

在研机构-

原研机构

Sumitomo Pharma Co., Ltd.

在研适应症-

非在研适应症

哮喘 [+1]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

UCB-35440

靶点

5-LOX x H1 receptor

作用机制

5-LOX抑制剂 [+1]

在研机构-

原研机构

UCB SA

在研适应症-

非在研适应症

哮喘

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 H1 receptor x 5-LOX 相关的临床结果

登录后查看更多信息

100 项与 H1 receptor x 5-LOX 相关的转化医学

登录后查看更多信息

0 项与 H1 receptor x 5-LOX 相关的专利（医药）

登录后查看更多信息

项与 H1 receptor x 5-LOX 相关的文献（医药）

2013-09-01·American Journal of Respiratory Cell and Molecular Biology1区 · 医学

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

1区 · 医学

Article

作者: Upadhyay, Swapna ; You, Ming ; Knoell, Daren L. ; Kostem, Emrah ; Berndt, Annerose ; Dopico, Richard A. ; Kaminski, Naftali ; Fabisiak, James P. ; Cario, Clinton ; Eskin, Eleazar ; Jang, An Soo ; Prows, Daniel R. ; Di, Y. P. Peter ; Vuga, Louis J. ; Ganguly, Koustav ; Brant, Kelly A. ; Martin, Timothy M. ; Liu, Pengyuan ; Concel, Vincent J. ; Leikauf, George D. ; Bein, Kiflai

In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Candidates were selected that contained a promoter SNP that could alter a putative transcription factor binding site and had variable expression by transcriptomic analyses. The latter two criteria also required that ≥10% of mice carried the minor allele and that this allele could account for ≥10% of the phenotypic difference noted between the strains at the phenotypic extremes. This integrative, functional approach revealed 14 candidate genes that included Atp1a1, Alox5, Galnt11, Hrh1, Mbd4, Phactr2, Plxnd1, Ptprt, Reln, and Zfand4, which had significant SNP associations, and Itga9, Man1a2, Mapk14, and Vwf, which had suggestive SNP associations. Of the genes with significant SNP associations, Atp1a1, Alox5, Plxnd1, Ptprt, and Zfand4 could be associated with ALI in several ways. Using a competitive electrophoretic mobility shift analysis, Atp1a1 promoter (rs215053185) oligonucleotide containing the minor G allele formed a major distinct faster-migrating complex. In addition, a gene with a suggestive SNP association, Itga9, is linked to transforming growth factor β1 signaling, which previously has been associated with the susceptibility to ALI in mice.

2008-06-01·Clinical & Experimental Allergy2区 · 医学

Histamine H1‐receptor antagonists inhibit nuclear factor‐kappaB and activator protein‐1 activities via H1‐receptor‐dependent and ‐independent mechanisms

2区 · 医学

Article

作者: C. Henriquet ; C. Gougat ; C. Roumestan ; A. Michel ; F. Bichon ; M. Mathieu ; K. Portet ; D. Jaffuel

SummaryBackground Histamine H1‐receptor antagonists are used to relieve the symptoms of an immediate allergic reaction. They have additional anti‐inflammatory effects that could result from an inhibition of the transcription factors activator protein‐1 (AP‐1) and nuclear factor‐kappa B (NF‐κB). The implication of the H1‐receptor in these effects is controversial. Diphenhydramine is a first‐generation H1‐receptor antagonist while mizolastine and desloratadine are second‐generation compounds. Mizolastine is also an inhibitor of 5‐lipoxygenase (5‐LO), an enzyme that has been involved in NF‐κB activation.Objective We measured the ability of antihistamines to reverse histamine‐induced smooth muscle contraction, an effect that involves the H1‐receptor. We then investigated whether these drugs affect NF‐κB and AP‐1 activities in A549 lung epithelial cells, and whether this potential regulation involves H1‐receptor and 5‐LO.Methods Muscle tone was measured on tracheal segments of guinea‐pigs. The H1‐receptor was overexpressed by transfection and detected by Western blotting and immunofluorescence microscopy. NF‐κB and AP‐1 activities were assessed by reporter gene assays in cells overexpressing or not overexpressing the H1‐receptor. Production of regulated upon activation, normal T cell expressed andsecreted (RANTES), a chemokine whose expression is induced through NF‐κB, was measured using an immunoassay.Results H1‐receptor antagonists reversed histamine‐induced contraction in a dose‐dependent manner. Induction of AP‐1 and NF‐κB activities by histamine and the down‐regulatory effect of antihistamines required overexpression of the H1‐receptor. In contrast, when tumour necrosis factor‐α and a phorbol ester were used to stimulate NF‐κB and AP‐1 activities, respectively, repression of these activities did not involve the H1‐receptor. Indeed, repression was triggered only by a subset of H1‐receptor antagonists and was not stronger after overexpression of the H1‐receptor. Mizolastine and desloratadine dose‐dependently decreased tumour necrosis factor‐α‐induced production of RANTES. Diphenhydramine, H2‐ and H3‐receptor antagonists as well as selective inhibitors of 5‐LO were ineffective in this assay.Conclusion Repression of NF‐κB and AP‐1 activities by H1‐receptor antagonists involves H1‐receptor‐dependent and ‐independent mechanisms but not 5‐LO.

2006-08-01·Current Opinion in Allergy & Clinical Immunology3区 · 医学

Genetic mechanism of aspirin-induced urticaria/angioedema

3区 · 医学

Review

作者: Lee, Soo-Keol ; Kim, Seung-Hyun ; Park, Hae-Sim ; Ye, Young-Min

PURPOSE OF REVIEWAspirin-induced urticaria/angioedema is a major aspirin-related hypersensitivity often associated with aspirin-intolerant asthma. Genetic studies on aspirin-intolerant asthma have shown chronic overproduction of cysteinyl leukotrienes. The genetic analysis of aspirin-induced urticaria/angioedema is limited, however.RECENT FINDINGSA recent study on HLA genotypes has suggested that the HLA alleles DRB11302 and DQB10609 may be genetic markers for aspirin-induced urticaria/angioedema. A polymorphism study that examined nine single-nucleotide polymorphisms of five leukotriene-related genes [ALOX5 (encoding 5-lipoxygenase), ALOX5AP (5-lipoxygenase-activating protein), PTGS2 (cyclooxygenase 2), LTC4S (leukotriene C4 synthase), and CYSLTR1 (cysteinyl leukotriene receptor 1)] found that promoter polymorphisms of ALOX5 (-1708A>G) and CYSLTR1 (-634C>T) were significantly different between aspirin-intolerant asthma and aspirin-induced urticaria/angioedema, suggesting different contributions to the lipoxygenase pathway. A second polymorphism study, conducted on histamine-related genes, did not find any significant associations with aspirin-induced urticaria/angioedema for the genes HNMT (encoding histamine N-methyltransferase), HRH1 or HRH2 (encoding histamine receptor types 1 and 2 respectively), or the gene encoding high-affinity IgE receptor Ibeta (FcepsilonRIbeta); however, the FcepsilonRIalpha gene promoter polymorphism was significantly associated with aspirin-induced urticaria/angioedema. This finding has been supported by in vitro functional studies.SUMMARYThe HLA alleles DRB11302 and DQB10609, and the ALOX5 and FcepsilonRIalpha promoter polymorphisms, may contribute to the pathogenesis of aspirin-induced urticaria/angioedema. Further investigation to identify candidate genetic markers would help to elucidate the pathogenic mechanism of this condition.